ArticleHuman molecular genetics2014
An ALS-mutant TDP-43 neurotoxic peptide adopts an anti-parallel β-structure and induces TDP-43 redistribution.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 54 citations in OpenAlex.
- Structural details of helix-mediated multimerization of the conserved region of TDP-43 C-terminal domain.Nature communications · 2025Article
- Review
- Uncovering Intermolecular Interactions Driving the Liquid-Liquid Phase Separation of the TDP-43 Low-Complexity Domain via Atomistic Dimerization Simulations.Journal of chemical information and modeling · 2024Article
- Molecular Mechanisms of Phase Separation and Amyloidosis of ALS/FTD-linked FUS and TDP-43.Aging and disease · 2024Review
- Synthetic β-sheets mimicking fibrillar and oligomeric structures for evaluation of spectral X-ray scattering technique for biomarker quantification.Cell & bioscience · 2024Article
- Protein aggregation and therapeutic strategies in SOD1- and TDP-43- linked ALS.Frontiers in molecular biosciences · 2024Review
- Degradation of neurodegenerative disease-associated TDP-43 aggregates and oligomers via a proteolysis-targeting chimera.Journal of biomedical science · 2023Article
- Molecular Dissection of TDP-43 as a Leading Cause of ALS/FTLD.International journal of molecular sciences · 2022Review
- Aging RNA granule dynamics in neurodegeneration.Frontiers in molecular biosciences · 2022Review
- Prionoids in amyotrophic lateral sclerosis.Brain communications · 2022Review
- The Different Faces of the TDP-43 Low-Complexity Domain: The Formation of Liquid Droplets and Amyloid Fibrils.International journal of molecular sciences · 2021Review
- Application of yeast to studying amyloid and prion diseases.Advances in genetics · 2020Review
- Amyotrophic Lateral Sclerosis: Proteins, Proteostasis, Prions, and Promises.Frontiers in cellular neuroscience · 2020Article
- TDP-43 induces mitochondrial damage and activates the mitochondrial unfolded protein response.PLoS genetics · 2019Article
- The role of liquid-liquid phase separation in aggregation of the TDP-43 low-complexity domain.The Journal of biological chemistry · 2019Article
- Structural Insights Into TDP-43 and Effects of Post-translational Modifications.Frontiers in molecular neuroscience · 2019Review
- Molecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis.Frontiers in molecular neuroscience · 2019Review
- Nucleo-cytoplasmic transport of TDP-43 studied in real time: impaired microglia function leads to axonal spreading of TDP-43 in degenerating motor neurons.Acta neuropathologica · 2018Article
- Atomic-level evidence for packing and positional amyloid polymorphism by segment from TDP-43 RRM2.Nature structural & molecular biology · 2018Article
- MiR-130a regulates neurite outgrowth and dendritic spine density by targeting MeCP2.Protein & cell · 2016Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
TDP-43 proteinopathies are clinically and genetically heterogeneous diseases that had been considered distinct from classical amyloid diseases. Here, we provide evidence for the structural similarity between TDP-43 peptides and other amyloid proteins. Atomic force microscopy and electron microscopy examination of peptides spanning a previously defined amyloidogenic fragment revealed a minimal core region that forms amyloid fibrils similar to the TDP-43 fibrils detected in FTLD-TDP brain tissues. An ALS-mutant A315E amyloidogenic TDP-43 peptide is capable of cross-seeding other TDP-43 peptides and an amyloid-β peptide. Sequential Nuclear Overhauser Effects and double-quantum-filtered correlation spectroscopy in nuclear magnetic resonance (NMR) analyses of the A315E-mutant TDP-43 peptide indicate that it adopts an anti-parallel β conformation. When added to cell cultures, the amyloidogenic TDP-43 peptides induce TDP-43 redistribution from the nucleus to the cytoplasm. Neuronal cultures in compartmentalized microfluidic-chambers demonstrate that the TDP-43 peptides can be taken up by axons and induce axonotoxicity and neuronal death, thus recapitulating key neuropathological features of TDP-43 proteinopathies. Importantly, a single amino acid change in the amyloidogenic TDP-43 peptide that disrupts fibril formation also eliminates neurotoxicity, supporting that amyloidogenesis is critical for TDP-43 neurotoxicity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.